A Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of SM04646 Inhalation Solution in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

NCT03591926 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: SM04646-IPF-03
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 6

Brief Summary

SM04646-IPF-03 is a Phase 2a, multi-center, open-label study evaluating the safety and efficacy of a single inhaled, nebulized dose of SM04646 solution over a 12-week treatment regimen in subjects with mild to moderate IPF. A total of approximately 24 subjects will be enrolled in the study (approximately 12 subjects into the "non-bronchoalveolar lavage \[BAL\]" arm and approximately 12 subjects into the "BAL" arm). Subjects that currently do not require, have failed to tolerate, or have opted not to have treatment with pirfenidone or nintedanib will have the option of participation in the "BAL" arm or participation in the "non-BAL" arm. Subjects currently receiving treatment with pirfenidone or nintedanib must be on stable treatment for a minimum of 12 weeks prior to the Screening Visit. Subjects currently on treatment with pirfenidone or nintedanib may participate in the "non-BAL" arm only. Eligible subjects will participate in a treatment period of 12 weeks and a follow-up period of 12 weeks. The treatment dosing pattern will follow a 2 weeks on, 2 weeks off regimen, wherein subjects will dose 5 consecutive days of each 7 day "on" week.

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

SM04646; IPF; nebulized; inhalation

Outcome Measures

Primary Outcomes (11)

• Safety and tolerability: treatment-emergent adverse events (TEAEs)

  Evaluate the safety and tolerability of SM04646 as measured by TEAEs during the entire treatment period

  Week 24

• Safety and tolerability: number of subjects with a clinically significant change from baseline in clinical laboratory tests

  Evaluate the safety and tolerability of SM04646 as measured by the number of subjects with a clinically significant change from baseline in clinical laboratory tests

  Week 24

• Safety and tolerability: number of subjects with a clinically significant change from baseline in vital signs

  Evaluate the safety and tolerability of SM04646 as measured by the number of subjects with a clinically significant change from baseline in vital signs

  Week 24

• Safety and tolerability: number of subjects with a clinically significant change from baseline in oxygen saturation

  Evaluate the safety and tolerability of SM04646 as measured by the number of subjects with a clinically significant change from baseline in oxygen saturation

  Week 24

• Safety and tolerability: number of subjects with a clinically significant change from baseline in electrocardiogram (ECG) parameters

  Evaluate the safety and tolerability of SM04646 as measured by the number of subjects with a clinically significant change from baseline in ECG parameters

  Week 24

• Plasma pharmacokinetics (PK): Cmax

  Measure maximum observed concentration of SM04646 (Cmax) in blood plasma

  Baseline and Week 10

• Plasma PK: tmax

  Measure time to SM04646 Cmax in blood plasma

  Baseline and Week 10

• Plasma PK: AUC

  Measure the area under the plasma concentration-time curve (AUC) for SM04646 in blood plasma

  Baseline and Week 10

• Plasma PK: t 1/2

  Measure the terminal phase half-life (t 1/2) of SM04646 in blood plasma

  Baseline and Week 10

• Plasma PK: accumulation ratio

  Measure the accumulation ration of SM04646 in blood plasma

  Baseline and Week 10

• Change from baseline in concentration of SM04646 in BAL fluid ("BAL" arm only)

  Measure concentration of SM04646 in BAL fluid prior to dosing and after two weeks of dosing

  Baseline and Week 2

Secondary Outcomes (11)

• Change from baseline of forced vital capacity (FVC) (% predicted)

  Baseline and Week 24

• Change from baseline of FVC (liters)

  Baseline and Week 24

• Categorical analysis of FVC (% predicted) change

  Baseline and Week 24

• Time to disease progression

  Week 24

• Change from baseline of forced expiratory volume in 1 second (FEV1) (% predicted)

  Baseline and Week 24

Study Arms (2)

"BAL" Arm

EXPERIMENTAL

Subjects in this arm will undergo a bronchoalveolar lavage (BAL) procedure at baseline and after two weeks of treatment.

Drug: SM04646

"Non-BAL" Arm

EXPERIMENTAL

Subjects in this arm will not undergo any BAL procedures.

Drug: SM04646

Interventions

SM04646 DRUG

Nebulized, inhaled solution; single dose concentration dosed once per day for 12 weeks; dosing pattern will follow a 2 weeks on, 2 weeks off regimen, wherein subjects will dose 5 consecutive days of each 7 day "on" week.

"BAL" Arm; "Non-BAL" Arm

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• IPF diagnosis within 5 years of study start based upon thoracic society guidelines and confirmed by Investigator at study start
• Able to walk \> 150 m in 6 Minute Walk Test without the use of supplemental oxygen at study start
• Has a life expectancy of at least 12 months in the opinion of the Investigator
• Full understanding of the requirements of the study and willingness and ability to comply with all study visits and procedures
• Able to comprehend and willing to sign an informed consent form (ICF) prior to any study-related procedure being performed
• Able to tolerate and complete placebo (vehicle) inhalation for 10 minutes without experiencing a significant cough, in the opinion of the Investigator
• Subjects currently treated with pirfenidone or nintedanib must be willing to remain on their current treatment for the duration of the protocol, unless they experience rapid progression, or if, in the opinion of the Investigator, treatment adjustments are necessary

You may not qualify if:

• Women who are pregnant or lactating
• Women of childbearing potential who are sexually active and are not willing to use an appropriate method of birth control during the study treatment period until 90 days post study medication administration
• Males who are sexually active and not willing to use a condom, and have a partner who is capable of becoming pregnant, if neither has had surgery to become sterilized, and/or who are not willing to use an appropriate method of birth control during the study treatment period until 90 days post study medication administration
• Males unwilling to refrain from sperm donation during the study treatment period until 90 days post study medication administration
• Subjects unwilling to refrain from blood and plasma donation during the study treatment period until 90 days post study medication administration
• A history of abuse of prescription or illicit drugs within 6 months prior to study start
• Positive urine drug and alcohol screen with the exception of positive findings related to current prescription therapy at study start
• Occurrence of serious illness requiring hospitalization within 90 days prior to study start
• Presence of active infections at study start
• Current smoker or past history of smoking (e.g., cigarettes, e-cigarettes, pipes, cigars) within 6 months of study start or \>50 pack years
• Use of non-inhaled tobacco- or nicotine-containing products (e.g., chewing tobacco, nicotine gum, lozenges, or patches) within 30 days prior to study start until completion of the study
• Regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (1 drink = 5 ounces \[150 mL\] of wine or 12 ounces \[360 mL\] of beer or 1.5 ounces \[45 mL\] of hard liquor) within 30 days prior to study start until completion of the study
• Lung transplantation anticipated during the duration of the trial
• Subjects receiving treatment with pirfenidone or nintedanib that:
• Have been on treatment for less than 12 weeks prior to study start

Sponsors & Collaborators

• Biosplice Therapeutics, Inc.: lead

Study Sites (6)

Research Site

Camperdown, New South Wales, Australia

Location

Research Site

Concord, New South Wales, Australia

Location

Research Site

Bedford Park, South Australia, Australia

Location

Research Site

Clayton, Victoria, Australia

Location

Research Site

Christchurch, New Zealand

Location

Research Site

Dunedin, New Zealand

Location

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Respiratory Aspiration

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Yusuf Yazici, M.D.

  Biosplice Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2018
• First Posted: July 19, 2018
• Study Start: January 1, 1900
• Primary Completion: January 1, 1900
• Study Completion: January 1, 1900
• Last Updated: October 9, 2018

Record last verified: 2018-10

Locations

NZ (2); AU (4)